Page 249 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 22: Pain Control, Sedation, and Use of Muscle Relaxants 153

from mild depression of responsiveness to obtundation. It is a potent easy to titrate for the desired effect up to 800 mg total daily dose.
anxiolytic as well as a potent amnestic agent that is dose dependent. Quetiapine undergoes hepatic metabolism via the CYP450 system
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Propofol has no analgesic properties. and produces an active metabolite N-desalkyl quetiapine that has a
Respiratory system: The CO response curve is blunted, and apnea half-life of approximately 9 to 12 hours.
2
may be seen, especially after a loading dose is given. The respira- Risperidone: It is available as a tablet, oral solution, and a long-acting
tory pattern is usually a decrease in tidal volume and an increase in intramuscular injection. Dosing can range from 0.5 to 3 mg one to
respiratory rate. two times daily for the oral formulations. The onset of sedation is
Cardiovascular system: Propofol can cause significant decreases in approximately 1 hour. Risperidone has extensive hepatic metabolism
blood pressure, especially in hypovolemic patients. This is mainly due via CYP2D6 and has an active metabolite, 9-hydroxy-risperidone
to preload reduction from dilation of venous capacitance vessels. A with an elimination half-life up to 30 hours.
lesser effect is mild myocardial depression. 78,79 Care must be taken in
giving this drug to patients with marginal cardiac function; however, Pharmacodynamics
since myocardial oxygen consumption is decreased by propofol and Central nervous system: These agents produce CNS depression, result-
the myocardial oxygen supply-demand ratio is preserved, it may be ing in a calm, often detached appearance. They are used most com-
useful in patients with ischemic heart disease. monly in critically ill patients who are acutely agitated and hyperactive.
Other effects: Because it is delivered in an intralipid carrier, hypertri- Patients may demonstrate a mental and psychiatric indifference to
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glyceridemia is a possible side effect. 80,81 Therefore, triglyceride levels the environment. Patients may also experience a state of cataleptic
should be checked at baseline and every 48 to 72 hours. If hyper- immobility. There is no demonstrable amnesia with these drugs. They
triglyceridemia occurs (>500 mg/dL), the drug should be stopped. have no effect on seizure activity. Analgesic effects are minimal.
Intralipid parenteral feedings should be adjusted according to the Respiratory system: These agents do not have any significant effect on
propofol infusion rate because there is a significant caloric load from the respiratory system when used alone. There are reports of attenu-
propofol (1 kcal/mL). Strict aseptic technique and frequent changing ation of respiratory depression in the presence of opiates, but this
of infusion tubing are essential to prevent iatrogenic transmission effect is mild.
of bacteria and fungi because propofol can support their growth. Cardiovascular system: Haloperidol may result in mild hypotension
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Dysrhythmias, heart failure, metabolic acidosis, hyperkalemia, and secondary to peripheral α -blocking effects. Haloperidol may also
1
rhabdomyolysis have been reported in both children and adults decrease the neurotransmitter function of dopamine and lead to mild
treated with propofol, especially at high doses (>80 μg/kg per minute hypotension by this mechanism. Haloperidol and the atypical anti-
in adults). Additionally, propofol can cause significant hypotension psychotics may prolong the QT interval and have been reported to
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due to systemic vasodilation and it is not recommended to administer result in torsade de pointes, although this problem is rare.
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as a bolus. Other effects: Extrapyramidal effects are seen occasionally with halo-
Antipsychotics: Antipsychotics such as haloperidol and “atypical” peridol but are much less common with intravenous than with oral
agents (eg, ziprasidone, olanzapine, quetiapine, and risperidone) are butyrophenones. When these complications occur, treatment with
used occasionally in the ICU for sedation. These drugs induce a state diphenhydramine or benztropine may be necessary. Neuroleptic
of tranquility such that patients often demonstrate a detached affect. malignant syndrome (NMS) occurs rarely and is characterized by
These drugs appear to antagonize the serotonin receptors 5-HT and “lead pipe” muscle rigidity, high fever, and mental status changes.
2a
5-HT , and block mesolimbic dopamine (DA) receptors over the The mechanism of NMS is not fully understood, although some
2C
nigrostriatal neurons. data suggest a central dopaminergic blockade that leads to extrapy-
ramidal side effects and muscle rigidity with excess heat generation.
Pharmacokinetics Bromocriptine, dantrolene, and pancuronium all have been used to
Haloperidol: After an intravenous dose, onset of sedation usually occurs treat NMS successfully. 86
after 2 to 5 minutes. The half-life is approximately 2 hours but is dose
dependent. Dose requirements vary widely, starting at 1 to 10 mg and ■
titrating to effect. Haloperidol undergoes hepatic metabolism. OTHER DRUGS USED FOR SEDATION IN THE ICU
Ziprasidone: It is an atypical antipsychotic and can be administered by Dexmedetomidine 87-89 is a selective α agonist approved for short-term
2
an intramuscular (IM) or oral route. For acute agitation the initial dose use (<24 hours) in patients initially receiving mechanical ventilation.
is 10 mg IM and can be repeated in 2 hours. Maximum daily dosing is While patients remain sedated when undisturbed, they arouse easily
40 mg. The onset of sedation is approximately 1 hour. Ziprasidone with stimulation. This drug is attractive because patients seem to
is extensively metabolized through CYP3A4 and CYP1A2 hepatic isoen- transition from sedated to awake states rather easily, thus facilitating
zymes and is dependent on liver function. There are four active metabo- neurologic examinations. The drug has both analgesic and anxiolytic
lites with an elimination half-life of 2 to 5 hours. effects. Side effects include bradycardia and hypotension, especially with
hypovolemia or high sympathetic tone.
Olanzapine: It is an atypical antipsychotic and is a potent antagonist of Ketamine has a molecular structure similar to phencyclidine. Patients
serotonin, dopamine, and α-receptors with intermediate antagonism given this drug experience a profound dissociative state. They may
against muscarinic receptors. It is available as an oral disintegrating keep their eyes open and maintain a protective cough reflex but appear
tablet, tablet, and an IM injection. With either formulation, the dose unaware of their surroundings. It is recommended to give this drug
is typically 10 mg once daily. In acute agitation, the IM dose can be slowly over a period of approximately 1 minute. Ketamine causes
repeated 2 to 4 hours after the initial injection. The onset of action minimal respiratory depression. There may be amnesia, but this is not
after injection is approximately 15 to 45 minutes and its half-life can a reliable property of the drug. Coordinated but seemingly purposeless
range from 21 to 54 hours. Smokers have an increased clearance up to movements are seen often. Profound analgesia is seen with ketamine.
40% and females have a 30% decreased clearance. Olanzapine under- The common side effect of emergence delirium and severe hallucina-
goes glucuronidation with cytochrome P450. Up to 40% of this drug tions has limited its usefulness for sedation of adult patients in the ICU.
is removed by first-pass metabolism. This phencyclidine derivative is popular as an illicit drug of abuse.
Quetiapine: It is only available in an oral formulation. Typical dosing Barbiturates such as thiopental and pentobarbital are potent agents
for delirium has been studied starting at 50 mg bid; however, there is a that cause amnesia and unconsciousness. They have little use as sedatives
high ceiling associated with quetiapine, which makes this medication in critically ill patients because of a propensity to cause hemodynamic

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